The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Cross-sectional analysis for lymphedema epidemiology in South Korea by HIRA data: An observational study.

Lymphedema is known to affect as many as 140 to 250 million people worldwide. Approximately 99% of lymphedemas are secondary cases after lymphadenectomy, radiation, or parasite infection. There has been no accurate estimate of the lymphedema population size in South Korea. This study aimed to quantify the epidemiology of lymphedema in South Korea and analyze the clinical characteristics of patients with lymphedema using a nationwide database. This large-scale cross-sectional study included patients who received one of the following three diagnostic codes - Q82.0 (hereditary lymphedema), I97.2 (breast cancer-related lymphedema), and I89.0 (unclassified lymphedema) from the Korean Health Insurance Review and Assessment service between January 2019 and July 2022 at tertiary hospitals, general hospitals, or other hospitals. The demographics of the lymphedema population, medication use, and medical characteristics were identified. Over the last 4 years, the annual incidence of lymphedema has steadily increased and peaked in 2021 with the number 1.85 out of 1000. Of all patients, 81% were located in the upper extremity, and 10.6% had previous cancer. Most patients were diagnosed in general hospitals (53.2%), at orthopedic surgery department (41.9%). On average, lymphedema patients spent 70.17 US dollar for medication and hospitalized for 16.9 days annually after diagnosis. Commonly prescribed medications were Entelon® (Vitis vinifera seed extract) (66.9%), steroids (40.5%), non-steroidal anti-inflammatory drugs (26.5%) and diuretics (21.8%). Only 5.7% of patients received surgery and 19.2% received herbal medicine. This is the first study in South Korea to quantify demographic and medical characteristics of lymphedema patients. These results will contribute to a comprehensive understanding of lymphedema diagnosis and treatment in our nation.

Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

PURPOSE: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. MATERIALS AND METHODS: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). RESULTS: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. CONCLUSIONS: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

PURPOSE: This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. MATERIALS AND METHODS: Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. RESULTS: The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. CONCLUSION: This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma.

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

The relationship between dementia caregivers and quality of life in South Korean populations.

The purpose of this study was to assess the relationship between quality of life and dementia caregivers. The 2019 Korean Community Health Survey participants were assessed using the Patient Health Questionnaire-9, subjective cognitive decline (SCD) and SCD-related functional limitation, and EuroQol 5-dimension (EQ-5D). Sociodemographic and psychosocial variables were evaluated and compared between participants with dementia caregivers (n = 37,614) and non-dementia caregivers (n = 140,518). The dementia caregivers group reported significantly higher rates of depression, SCD, SCD-related functional restriction, and mean EQ-5D compared to the non-dementia caregivers group (P < .001). After adjusting for multiple confoundings, the odds ratio (OR) for depression (Patient Health Questionnaire-9 ≥ 10), SCD, SCD-related functional limitation, and lowest quartile of the EQ-5D index scores in the dementia caregivers group were 1.43 (95% confidence interval [CI], 1.29-1.59), 1.30 (95% CI: 1.24-1.36), 1.26 (95% CI: 1.20-1.32), and 1.22 (95% CI: 1.16-1.29), respectively. Physical activity (OR: 1.47; 95% CI: 1.43-1.52), self-control (OR: 1.41; 95% CI: 1.35-1.47), daily activity (OR: 1.55; 95% CI: 1.50-1.60), pain (OR: 1.62; 95% CI: 1.58-1.67), and anxiety/depression (OR: 2.17; 95% CI: 2.10-2.24) were all more common among participants in the dementia caregivers group than in the non-dementia family caregivers group. Depression, SCD, and a lower quality of life are linked to dementia caregivers, especially if there is moderate to severe anxiety or depression.

Comprehensive Evaluation of OATP- and BCRP-Mediated Drug-Drug Interactions of Methotrexate Using Physiologically-Based Pharmacokinetic Modeling.

Methotrexate (MTX) is an antifolate agent widely used for treating conditions such as rheumatoid arthritis and hematologic cancer. This study aimed to quantitatively interpret the drug-drug interactions (DDIs) of MTX mediated by drug transporters using physiologically-based pharmacokinetic (PBPK) modeling. An open-label, randomized, 4-treatment, 6-sequence, 4-period crossover study was conducted to investigate the effects of rifampicin (RFP), an inhibitor of organic anionic transporting peptides (OATP) 1B1/3, and febuxostat (FBX), an inhibitor of breast cancer resistance protein (BCRP), on the pharmacokinetics of MTX in healthy volunteers. PBPK models of MTX, RFP, and FBX were developed based on in vitro and in vivo data, and the performance of the simulation results for final PBPK models was validated in a clinical study. In the clinical study, when MTX was co-administered with RFP or FBX, systemic exposure of MTX increased by 33% and 17%, respectively, compared with that when MTX was administered alone. When MTX was co-administered with RFP and FBX, systemic exposure increased by 52% compared with that when MTX was administered alone. The final PBPK model showed a good prediction performance for the observed clinical data. The PBPK model of MTX was well developed in this study and can be used as a potential mechanistic model to predict and evaluate drug transporter-mediated DDIs of MTX with other drugs.

Quantitative Evaluation of the Real-World Harmonization Status of Laboratory Test Items Using External Quality Assessment Data.

Background: In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests. Methods: We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels. Results: Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level. Conclusions: We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.

Clinical Manifestations of Malignant Struma Ovarii: A Retrospective Case Series in a Tertiary Hospital in Korea.

BACKGRUOUND: Malignant struma ovarii (MSO) is a very rare disease in which thyroid cancer originates from the ovary. Because it is rare for endocrinologists to encounter patients with MSO, endocrinologists may have a limited understanding of the disease. Therefore, we analyzed and introduced its incidence and clinical course in a tertiary hospital in Korea. METHODS: We retrospectively investigated the clinical data of 170 patients who underwent surgery for struma ovarii at the Department of Obstetrics and Gynecology of Samsung Medical Center from 1994 to May 2023. RESULTS: Among 170 patients with struma ovarii, 15 (8.8%) were diagnosed with MSO. The median age of patients with MSO was 48 years (range, 30 to 74), and the median tumor size was 3.3 cm (range, 0.5 to 11.0). Papillary thyroid carcinoma (46.7%) was the most common subtypes followed by follicular thyroid carcinoma (26.7%). All patients were diagnosed after surgery, with no predictions from preoperative imaging. The surgical extent of gynecological surgery was variable. Four patients (26.7%) underwent thyroidectomy for thyroid cancer, while one underwent total thyroidectomy and radioactive iodine therapy for MSO with peritoneal metastasis. Except for one patient who underwent hemithyroidectomy, thyroid stimulating hormone suppression therapy was performed in four patients. Only 53% of MSO patients were consulted by an endocrinologist. With a median follow-up period of 33 months (range, 4 to 156), 11 patients remained disease-free, one experienced progression with peritoneal seeding, and the remaining one was in treatment. There have been no recurrences or deaths due to MSO. CONCLUSION: An endocrinologist should be involved in establishing a therapeutic plan for MSO, for which the overall prognosis is generally favorable.

The Efficacy and Safety of Radiation-Free Retrograde Intrarenal Surgery: A Prospective Multicenter-Based, Randomized, Controlled Trial.

PURPOSE: Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management. MATERIALS AND METHODS: From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test. RESULTS: Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12]). CONCLUSIONS: This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

Detection of measles vaccine virus and measles-specific immunoglobulin M in children vaccinated against measles-mumps-rubella during measles outbreak.

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study.

Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults. Resting-state fMRI scans were acquired in 13 participants at baseline and during a 30 min hypertonic saline infusion (HSI). We used a seed-based approach to analyze the data, focusing on the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) as regions of interest (ROIs). Blood chemistry and perceived thirst were assessed pre- and post-infusion. As expected, serum sodium increased from pre- to post-infusion in the HSI group. The primary finding of this pilot study was that the functional connectivity between the SFO and a cluster within the OVLT increased from baseline to the late-phase of the HSI. Bidirectional connectivity changes were found with cortical regions, with some regions showing increased connectivity with sodium-sensing regions while others showed decreased connectivity. Furthermore, the functional connectivity between the SFO and the posterior cingulate cortex (a control ROI) did not change from baseline to the late-phase of the HSI. This finding indicates a distinct response within the NaCl sensing network in the human brain specifically related to acute hypernatremia that will need to be replicated in large-scale studies.

Androgen deprivation alone versus combined with pelvic radiation for adverse events and quality of life in clinically node-positive prostate cancer.

The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.

Automated CT quantification of interstitial lung abnormality in patients with resectable stage I non-small cell lung cancer: Prognostic significance.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), interstitial lung abnormalities (ILA) have been linked to mortality and can be identified on computed tomography (CT) scans. In the present study we aimed to evaluate the predictive value of automatically quantified ILA based on the Fleischner Society definition in patients with stage I NSCLC. METHODS: We retrospectively reviewed 948 patients with pathological stage I NSCLC who underwent pulmonary resection between April 2009 and October 2022. A commercially available deep learning-based automated quantification program for ILA was used to evaluate the preoperative CT data. The Fleischner Society definition, quantitative results, and interdisciplinary discussion led to the division of patients into normal and ILA groups. The sum of the fibrotic and nonfibrotic ILA components constituted the total ILA component and more than 5%. RESULTS: Of the 948 patients with stage I NSCLC, 99 (10.4%) patients had ILA. Shorter overall survival and recurrence-free survival was associated with the presence of ILA. After controlling for confounding variables, the presence of ILA remained significant for increased risk of death (hazard ratio [HR] = 3.09; 95% confidence interval [CI]: 1.91-5.00; p < 0.001) and the presence of ILA remained significant for increased recurrence (HR = 1.96; 95% CI: 1.16-3.30; p = 0.012). CONCLUSIONS: The automated CT quantification of ILA, based on the Fleischner Society definition, was significantly linked to poorer survival and recurrence in patients with stage I NSCLC.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

The Impact of the COVID-19 Pandemic on Bell's Palsy and Ramsay-Hunt Syndrome: A Multicenter Retrospective Study.

BACKGROUND: This article presents a comprehensive review of data on the impact of facial palsy during the coronavirus disease 2019 (COVID-19) pandemic. The possible causes and pathophysiological mechanisms of changes in the epidemiology of facial palsy during the COVID-19 pandemic are also discussed. METHODS: This multicenter retrospective cohort study included 943 patients diagnosed with Bell's palsy or Ramsay Hunt syndrome. This study compared patient demographics, comorbidities, symptoms, and treatments before the COVID-19 pandemic (from 2017 to 2019) and during the COVID-19 pandemic, from 2020 to 2022). RESULTS: Following the COVID-19 outbreak, there has been a significant increase in the number of cases of Bell's palsy, particularly among elderly individuals with diabetes. Bell's palsy increased after the COVID-19 outbreak, rising from 75.3% in the pre-COVID-19 era to 83.6% after the COVID-19 outbreak. The complete recovery rate decreased from 88.2% to 73.9%, and the rate of recurrence increased from 2.9% to 7.5% in patients with Bell's palsy. Ramsay Hunt syndrome showed fewer changes in clinical outcomes. CONCLUSION: This study highlights the impact of the COVID-19 pandemic on the presentation and management of facial palsy, and suggests potential associations with COVID-19. Notably, the observed increase in Bell's palsy cases among elderly individuals with diabetes emphasizes the impact of the pandemic. Identifying the epidemiological changes in facial palsy during the COVID-19 pandemic has important implications for assessing its etiology and pathological mechanisms of facial palsy disease.

Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.